Journal of Pharmaceutical Research International

Dimethylamine (DMA) and sodium nitrite (NaNO₂) are present in numerous foods, food additive and environmental factors, which enhance chemical driven liver damage by inducing oxidative stress and cellular injury. Therefore, this study evaluated the possible therapeutic and protective effects of selected plant extracts on dimethylamine (DMA) and sodium nitrite (NaNO₂)-induced hepatotoxicity in mice.

The selected plants (Morinda lucida, Securine gavirosa, Xylopia aethiopica, Piper guineense and Calotropis procera) were extracted by maceration in distilled water and concentrated using freeze dryer. Swiss male albino mice were divided into  Group I (control group) received distilled water; group II were administered orally with DMA (150 mg/kg body weight) and NaNO₂ (100 mg/kg body weight) twice every  week for 4 weeks, group III were treated orally with  extract every 48 hrs simultaneously with DMA and NaNO2  and continued until the end of the experiment, group IV  were treated orally with extract and fractions (150 mg/kg body weight) every 48 hrs for four weeks after the administration of DMA and NaNO2  and continued until the end of the experiment (4 weeks) and group V were given 5-flourouracil every 48 hours after induction of liver toxicity in mice. Liver function (alanine amino transferase, aspartate amino transferase, gamma glutamyl transferase and alkaline phosphatase) tests were done in the serum of mice using standard method. Extract of P. guineense exhibited the best activity and was fractionated for further hepatoprotective studies. Liver sections of the mice treated with fractions of P. guineense were used for immuno-histochemical studies for p53, BCl-2, COX-2 and Ki-67 expression, and liver histological analysis. The antioxidant status of the mice treated with fractions of P. guineense was determined by measuring the catalase activity, sodium dismutase activity, reduced glutathione and malondialdehyde concentrations in the liver homogenates. Data were expressed as mean and considered significant at p<0.05 by one-way Analysis of Variance using Graph Pad Prism 5.

The results of this study showed that activities of liver enzymes were significantly (p<0.05) decreased in groups treated with aqueous extracts after liver toxicity induction in mice. Treatment with fractions of P. guineense enhanced the antioxidant status of the mice administered with DNA/NaNO₂. Oral administration of fractions of P. guineense to mice conferred hepatoprotection as evident from normal serum enzyme levels and reduced injuries on hepatocytes. Immuno-histochemical analysis of the liver samples revealed reduction in the expression of anti-apoptotic protein BCl₂ and COX-2 in the mice treated with fractions of P. guineense and non-expression of cell cycle regulator p53 and Ki-67 after toxicity induction in mice.

The ability of the selected extracts and fractions of P. guineense to impose certain ameliorative effects on DMA and NaNO₂ induced toxicities in mice provided some scientific basis for their use in traditional medicine.  The extracts might be used for liver toxicity treatment and/or prevention.